iMSC exosome delivers hsa-mir-125b-5p and strengthens acidosis resilience through suppression of ASIC1 protein in cerebral ischemia-reperfusion.

Acid-sensing ion channel 1 (ASIC1) is critical in acidotoxicity and significantly contributes to neuronal death in cerebral stroke. Pharmacological inhibition of ASIC1 has been shown to reduce neuronal death. However, the potential of utilizing exosomes derived from pluripotent stem cells to achieve inhibition of Asic1 remains to be explored. Developing qualified exosome products with precise and potent active ingredients suitable for clinical application is also ongoing. Here, we adopt small RNA-seq to interrogate the miRNA contents in exosomes of pluripotent stem cell induced mesenchymal stem cell (iMSC). RNA-seq was used to compare the oxygen-glucose deprivation-damaged neurons before and after the delivery of exosomes. We used Western blot to quantify the Asic1 protein abundance in neurons before and after exosome treatment. An in vivo test on rats validated the neuroprotective effect of iMSC-derived exosome and its active potent miRNA hsa-mir-125b-5p. We demonstrate that pluripotent stem cell-derived iMSCs produce exosomes with consistent miRNA contents and sustained expression. These exosomes efficiently rescue injured neurons, alleviate the pathological burden, and restore neuron function in rats under oxygen-glucose deprivation stress. Furthermore, we identify hsa-mir-125b-5p as the active component responsible for inhibiting the Asic1a protein and protecting neurons. We validated a novel therapeutic strategy to enhance acidosis resilience in cerebral stroke by utilizing exosomes derived from pluripotent stem cells with specific miRNA content. This holds promise for cerebral stroke treatment with the potential to reduce neuronal damage and improve clinical patient outcomes.

Study on O3-NOx-VOCs combined air pollution and ozone health effects in the Hexi Corridor.

In order to study the ecological and atmospheric recovery of the Hexi Corridor region, this paper analyzes the migration changes of land use characteristics and utilizes multivariate data and BenMAP-CE software to study the pollution characteristics of ozone and its precursors and the impact on human health in the Hexi Corridor region. The results showed that the increase of cultivated land area in the Hexi Corridor mainly originated from grassland. The MDA8-O3 concentrations met the primary and secondary standards of the Ambient Air Quality Standards on 43% and 99% of the days, respectively. NO2 showed a negative weekend effect with O3, and HCHO was opposite to it. Temperature, barometric pressure, and vegetation were highly correlated with O3-NO2-HCHO. Ozone pollution in the study area caused about 60% of all-cause premature deaths due to cardiovascular diseases. The study suggests that controlling exogenous transport in Wuwei City during the high ozone period (except August) is mainly dominated by the west and northwest, and that synergistic management of VOCs and NOx emissions can reduce O3 pollution and, consequently, reduce the risk to human health.

Engagement-free and Contactless Bed Occupancy and Vital Signs Monitoring.

This paper presents the design and evaluation of an engagement-free and contactless vital signs and occupancy monitoring system called BedDot. While many existing works demonstrated contactless vital signs estimation, they do not address the practical challenge of environment noises, online bed occupancy detection and data quality assessment in the realworld environment. This work presents a robust signal quality assessment algorithm consisting of three parts: bed occupancy detection, movement detection, and heartbeat detection, to identify high-quality data. It also presents a series of innovative vital signs estimation algorithms that leverage the advanced signal processing and Bayesian theorem for contactless heart rate (HR), respiration rate (RR), and inter-beat interval (IBI) estimation. The experimental results demonstrate that BedDot achieves over 99% accuracy for bed occupancy detection, and MAE of 1.38 BPM, 1.54 BPM, and 24.84 ms for HR, RR, and IBI estimation, respectively, compared with an FDA-approved device. The BedDot system has been extensively tested with data collected from 75 subjects for more than 80 hours under different conditions, demonstrating its generalizability across different people and environments.

Analysis of human health effects under ozone exposure in the oasis area of Hetao Plain.

This article, based on OMI data products, utilizes spatial distribution, ozone-sensitive control areas, Pearson correlation methods, and the Ben-MAP model to study the changes in ozone column concentration from 2018 to 2022, along with the influencing factors and the health of populations exposed to ozone. The findings suggest a spatial variation in the ozone column concentration within the study area, with an increasing trend observed from west to east and from south to north. Over time, the ozone column concentration exhibits an initial increase followed by a subsequent decrease, with the peak concentration observed in 2019 at 37.45 DU and the nadir recorded in 2022 at 33.10 DU. The monthly mean distribution exhibits an inverted V-shaped pattern during the warm season from April to September, with a peak in July (46.71 DU) and a trough in April (35.29 DU). The Hetao Plain Oasis area is primarily a NOx control area in sensitive control areas. The concentrations of O3 and precursor HCHO exhibited significant positive correlations with vegetation index and air temperature, while showing significant negative correlations with wind speed and air pressure. The precursor NO2, in contrast, exhibited a significant negative correlation with both the vegetation index and relative humidity. Based on the ground-based monitoring sites and analysis of human health benefits, the study area witnessed 1944.45 deaths attributed to warm season O3 exposure in 2018, with a subsequent reduction in premature deaths by 149.7, 588.2, and 231.75 for the years 2019 to 2021 respectively when compared to the baseline year. In 2021, the observed decrease in warm-season O3 concentration within that region compared to 2018 resulted in a significant reduction, leading to the prevention of 126 premature deaths.

Expression of Serum Anti-BP180/230 Antibodies in Bullous Pemphigoid Patients Combined with Nervous System Diseases and Relevant Factor Analysis.

OBJECTIVE: To explore the anti-BP230/180 and anti-BP180 antibodies in patients with bullous pemphigoid (BP) combined with neurological diseases, and to analyse the relevant factors. STUDY DESIGN: Analytical study. Place and Duration of the Study: Neurology Department, Cangzhou People's Hospital, Cangzhou, from April 2019 to June 2022. METHODOLOGY: Eighty BP patients were chosen based on associated neurological diseases, they were split into single (n=42) and combined groups (n=38). Expression of anti-BP180/230 antibodies was compared between the two groups. Associations with neurological diseases were analysed and the factors affecting the expression of anti-BP180/230 antibodies were explored. RESULTS: Out of 80 patients, 61 were positive for anti-BP180 antibodies and 58 were positive for anti-BP230 antibodies. The proportion of patients with positive anti-BP230/180 antibodies in the single group was considerably lower than in the combined group (p<0.05). Presence of both nervous system diseases and BP was found to be associated with the presence of anti-BP230/180 antibodies (p<0.001). Univariate analysis showed statistically significant association with age (<70 years, total IgE (>100 IU/ml), and EOS count >0.5 x 109/L (p<0.05). Logistic analysis demonstrated that age, total IgE and EOS count were independent risk factors affecting the expression of anti-BP180 and anti-BP23 antibodies (p<0.05). CONCLUSION: Serum anti-BP230/180 antibodies expression is abnormally high in BP patients having nervous system diseases. Combined nervous system diseases, age, total IgE and EOS count are independent risk factors affecting expression of anti-BP180/230 antibodies. KEY WORDS: Anti-BP180 antibody, Anti-BP230 antibody, Bullous pemphigoid, Nervous system diseases.

Analysis of variation characteristics, transport paths, and influencing factors of atmospheric NO2 pollution in Western Europe.

Climate change and air pollution are one of the global environmental problems. It is significant to grasp the air pollution situation of Western Europe in recent 10 years for its or the global pollution control. Based on the OMI tropospheric nitrogen dioxide (NO2) column density data, the spatial and temporal distribution characteristics, variation trend, transmission path, and influencing factors of NO2 in 15 countries in Western Europe from 2011 to 2022 are discussed in this paper. Meanwhile, the annual average spatial and temporal distribution in 2023 is predicted by the random forest (RF) model. The results showed that (1) the 12-year spatial distribution map showed an increasing trend from southwest to northeast, with the border area of the Netherlands and Germany and Milan as two high-value areas, and the overall trend over time was that the high-concentration area gradually shrank, the low-concentration area gradually expanded, and the annual average concentration gradually decreased. (2) The inter-month trend presents a "U" shape, with the mean NO2 pollution ranking in winter > autumn > spring > summer. (3) Natural factors are one of the reasons affecting NO2; for instance, NO2 pollution has a strong positive correlation with the lifted index, relative humidity, and wind speed and a moderately strong negative correlation with precipitable water and air temperature. (4) Exogenous atmospheric transport is another important factor affecting the change of NO2 pollution in Western Europe. The HYSPLIT model is used to analyze the backward trajectory of Milan, Italy, and Nijmegen, Netherlands, in the four seasons of 2022. Both are mainly influenced by westerly airflows, and therefore, the transport effect in the atmosphere brings air pollutants from westerly regions in the atmosphere.

Structural and spectroscopic characterization of RufO indicates a new biological role in rufomycin biosynthesis.

Rufomycins constitute a class of cyclic heptapeptides isolated from actinomycetes. They are secondary metabolites that show promising treatment against Mycobacterium tuberculosis infections by inhibiting a novel drug target. Several nonproteinogenic amino acids are integrated into rufomycins, including a conserved 3-nitro-tyrosine. RufO, a cytochrome P450 (CYP)-like enzyme, was proposed to catalyze the formation of 3-nitro-tyrosine in the presence of O2 and NO. To define its biological function, the interaction between RufO and the proposed substrate tyrosine is investigated using various spectroscopic methods that are sensitive to the structural change of a heme center. However, a low- to high-spin state transition and a dramatic increase in the redox potential that are commonly found in CYPs upon ligand binding have not been observed. Furthermore, a 1.89-Å crystal structure of RufO shows that the enzyme has flexible surface regions, a wide-open substrate access tunnel, and the heme center is largely exposed to solvent. Comparison with a closely related nitrating CYP reveals a spacious and hydrophobic distal pocket in RufO, which is incapable of stabilizing a free amino acid. Molecular docking validates the experimental data and proposes a possible substrate. Collectively, our results disfavor tyrosine as the substrate of RufO and point to the possibility that the nitration occurs during or after the assembly of the peptides. This study indicates a new function of the unique nitrating enzyme and provides insights into the biosynthesis of nonribosomal peptides.

Differential regulation of mRNA stability modulates transcriptional memory and facilitates environmental adaptation.

Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Chromatin organization has been shown to play a role in the faster response of primed cells. However, the contribution of post-transcriptional regulation is not yet explored. Here we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose. We find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. Our work shows that gene-specific differences in intrinsic nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that primed cells present altered levels of RNA degradation machinery and that both nuclear and cytoplasmic mRNA decay modulate transcriptional memory. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory.

Surprising Hydrophobic Polymer Surface with a High Content of Hydrophilic Polar Groups.

The wetting property of a solid surface has been a hotspot for centuries, and many studies suggest that the hydrophobicity is highly related to the polar components. However, the underlying mechanism of polar moieties on the hydrophobicity remains unclear. Here, we tailor the surface polar moieties of epoxy resin (EP) by ozone modification and assess their wetting properties. Our results show that, for the modified EP with more (60.54%) polar moieties, the polar effect on hydrophobicity cannot be empirically observed. To reveal the underlying mechanism, the absorption parameters, including equilibrium distance, adsorption radius, and effective adsorption sites for water on EP before and after ozone treatment, are calculated on the basis of molecular simulations. After ozone modification, the equilibrium distance (from 1.95 to 1.70 Å), adsorption radius (from 3.80 to 4.50 Å), and effective adsorption sites (from 1 to 2) change slightly and the EP surface remains hydrophobic, although the polar groups significantly increase. Therefore, it is concluded that the wetting properties of solid surfaces are dominated by the equilibrium distance, adsorption radius, and effective adsorption sites for water on solids, and the nonlinear relationship between polar groups and hydrophilicity is clarified.

Using TIF-Seq2 to investigate association between 5´ and 3´mRNA ends.

The development of high-throughput technologies has revealed pervasive transcription in all genomes that have been investigated so far. This has uncovered a highly interleaved transcriptome organization involving thousands of overlapping coding and non-coding RNA isoforms that challenge our traditional definitions of genes and functional regions of the genome. In this chapter, we discuss the application of an improved Transcript Isoform Sequencing approach (TIF-Seq2) able to concurrently determine the start and end sites of individual RNA molecules. We exemplify its use for the investigation of the human transcriptome and show how it is especially well suited to discriminate between overlapping molecules and accurately define their boundaries.

Deep learning algorithms for brain disease detection with magnetic induction tomography.

PURPOSE: In order to improve the reconstruction accuracy of magnetic induction tomography (MIT) and achieve fast imaging especially in the detection of cerebral hemorrhage, artificial intelligence algorithms are proposed to improve the accuracy of MIT inverse problem. METHODS: According to the standard geometric data of human head, a three-dimensional (3D) head model containing four layer tissues is established for brain image reconstruction of MIT. Four deep learning (DL) networks, including restricted Boltzmann machine (RBM), deep belief network (DBN), stacked autoencoder (SAE), and denoising autoencoder (DAE), are used to solve the nonlinear reconstruction problem of MIT, and the reconstruction results of DL networks and back-projection algorithm are compared. Finally, in order to verify the practical value of DL algorithms, the phantom experiment is carried out with MIT detection system. RESULTS: Using the nonlinear data learning ability of DL algorithms, the rapid and high-precision imaging of cerebral hemorrhage can be realized. Compared with the back-projection algorithm, the DL improves the artifact and the accuracy of the reconstruction image. The location and volume of bleeding can be reconstructed and the prediction time reaches 20 ms. Moreover, the anti-noise performance of the networks can reach 20 dB. CONCLUSIONS: The DL can effectively improve the reconstruction accuracy and prediction speed of the image when it is applied to the reconstruction of cerebral hemorrhage in MIT. This feasibility study MIT to be a potential technology for brain diseases to fully meet the needs of accurate, rapid, and low-cost clinical diagnosis and continuous monitoring.

Technologies for magnetic induction tomography sensors and image reconstruction in medical assisted diagnosis: A review.

Magnetic induction tomography (MIT) is a non-invasive and non-contact imaging technology, which can be used in medical diagnosis by reconstructing the electrical distribution of biological tissues. Unlike other large medical imaging equipment, the device of MIT is with small size and low cost. The theoretical basis of MIT is by measuring the phase difference of magnetic flux density generated around the imaging objects, analyzing the eddy current distribution, and then using the reconstruction algorithms to obtain the electrical characteristic distribution of the object. This review introduces the development of imaging systems and the reconstruction algorithms of MIT as a medical assisted diagnostic technology, including the optimal design of the sensors, the excitation methods of the system, the calculation methods of the eddy current, and the improved methods of different reconstruction algorithms.

Design of a scanning magnetic induction phase measurement system for respiratory monitoring.

The commonly used respiratory monitoring methods in clinical medicine are chest belt or ventilators, which are not easy to carry and cumbersome to operate. In order to solve this problem, a low-cost and portable magnetic induction phase detection system for respiratory monitoring is proposed. In this study, a magnetic induction tomography system for respiration detection is established, and the phase sensitivity of the system to conductive object is evaluated through a series of experiments. At the same time, phantom experiments are carried out to simulate the respiratory process, and the phase monitoring indicators are collected to describe different respiratory states. The experimental results show that the phase detection results are consistent with the changes in the respiratory cycle. The signal-to-noise ratio of the system is 79 dB. It proves the feasibility of using magnetic induction phase measurement in respiratory monitoring and provides a new detection method of respiratory monitoring.

TIF-Seq2 disentangles overlapping isoforms in complex human transcriptomes.

Eukaryotic transcriptomes are complex, involving thousands of overlapping transcripts. The interleaved nature of the transcriptomes limits our ability to identify regulatory regions, and in some cases can lead to misinterpretation of gene expression. To improve the understanding of the overlapping transcriptomes, we have developed an optimized method, TIF-Seq2, able to sequence simultaneously the 5' and 3' ends of individual RNA molecules at single-nucleotide resolution. We investigated the transcriptome of a well characterized human cell line (K562) and identified thousands of unannotated transcript isoforms. By focusing on transcripts which are challenging to be investigated with RNA-Seq, we accurately defined boundaries of lowly expressed unannotated and read-through transcripts putatively encoding fusion genes. We validated our results by targeted long-read sequencing and standard RNA-Seq for chronic myeloid leukaemia patient samples. Taking the advantage of TIF-Seq2, we explored transcription regulation among overlapping units and investigated their crosstalk. We show that most overlapping upstream transcripts use poly(A) sites within the first 2 kb of the downstream transcription units. Our work shows that, by paring the 5' and 3' end of each RNA, TIF-Seq2 can improve the annotation of complex genomes, facilitate accurate assignment of promoters to genes and easily identify transcriptionally fused genes.

The RNA exosome shapes the expression of key protein-coding genes.

The ribonucleolytic exosome complex is central for nuclear RNA degradation, primarily targeting non-coding RNAs. Still, the nuclear exosome could have protein-coding (pc) gene-specific regulatory activities. By depleting an exosome core component, or components of exosome adaptor complexes, we identify ∼2900 transcription start sites (TSSs) from within pc genes that produce exosome-sensitive transcripts. At least 1000 of these overlap with annotated mRNA TSSs and a considerable portion of their transcripts share the annotated mRNA 3' end. We identify two types of pc-genes, both employing a single, annotated TSS across cells, but the first type primarily produces full-length, exosome-sensitive transcripts, whereas the second primarily produces prematurely terminated transcripts. Genes within the former type often belong to immediate early response transcription factors, while genes within the latter are likely transcribed as a consequence of their proximity to upstream TSSs on the opposite strand. Conversely, when genes have multiple active TSSs, alternative TSSs that produce exosome-sensitive transcripts typically do not contribute substantially to overall gene expression, and most such transcripts are prematurely terminated. Our results display a complex landscape of sense transcription within pc-genes and imply a direct role for nuclear RNA turnover in the regulation of a subset of pc-genes.

Transcript isoform sequencing reveals widespread promoter-proximal transcriptional termination in Arabidopsis.

RNA polymerase II (RNAPII) transcription converts the DNA sequence of a single gene into multiple transcript isoforms that may carry alternative functions. Gene isoforms result from variable transcription start sites (TSSs) at the beginning and polyadenylation sites (PASs) at the end of transcripts. How alternative TSSs relate to variable PASs is poorly understood. Here, we identify both ends of RNA molecules in Arabidopsis thaliana by transcription isoform sequencing (TIF-seq) and report four transcript isoforms per expressed gene. While intragenic initiation represents a large source of regulated isoform diversity, we observe that ~14% of expressed genes generate relatively unstable short promoter-proximal RNAs (sppRNAs) from nascent transcript cleavage and polyadenylation shortly after initiation. The location of sppRNAs correlates with the position of promoter-proximal RNAPII stalling, indicating that large pools of promoter-stalled RNAPII may engage in transcriptional termination. We propose that promoter-proximal RNAPII stalling-linked to premature transcriptional termination may represent a checkpoint that governs plant gene expression.

System-wide Profiling of RNA-Binding Proteins Uncovers Key Regulators of Virus Infection.

The compendium of RNA-binding proteins (RBPs) has been greatly expanded by the development of RNA-interactome capture (RIC). However, it remained unknown if the complement of RBPs changes in response to environmental perturbations and whether these rearrangements are important. To answer these questions, we developed "comparative RIC" and applied it to cells challenged with an RNA virus called sindbis (SINV). Over 200 RBPs display differential interaction with RNA upon SINV infection. These alterations are mainly driven by the loss of cellular mRNAs and the emergence of viral RNA. RBPs stimulated by the infection redistribute to viral replication factories and regulate the capacity of the virus to infect. For example, ablation of XRN1 causes cells to be refractory to SINV, while GEMIN5 moonlights as a regulator of SINV gene expression. In summary, RNA availability controls RBP localization and function in SINV-infected cells.

The application of small organic π-conjugated discotic derivatives in photoacoustic imaging and photothermal conversion.

Near-infrared absorbing dyes are catching people's attention as they are committed to find materials with greater photoacoustic (PA) and photothermal (PT) effect. In this study, a new series of organic π-conjugated discotic derivatives synthesized via [2 + 2] click chemistry were introduced. The PA intensity and PT conversion effect of the derivatives were monitored. It was found that the π-conjugated discotic derivatives had a proper absorption peak and PA intensity by introducing the click regents. Furthermore, the PA intensity remained relatively high, while B12 molecules were embedded in hydrophobic phospholipid bilayer of liposomes (B12⊂L). The application in biological therapy for tumors become possible as the toxicity of B12⊂L was low. What's more, when B12 molecules embedded in poly (N-isopropylacrylamide)-block-poly (2-nitrobenzyl methacrylate) (PNIPAM-b-PNBM) thermosensitive micelles were irradiated by laser, the molecules could take the place of direct temperature stimulus. This work affords us a way to solve the problem in which direct temperature stimulus is inapplicable.

Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model.

The induced pluripotent stem cell (iPSC) technology has provided a unique opportunity to develop disease-specific models and personalized treatment for genetic disorders, and is well suitable for the study of Werner syndrome (WS), an autosomal recessive disease with adult onset of premature aging caused by mutations in the RecQ like helicase (WRN) gene. WS-derived fibroblasts were previously shown to be able to generate iPSCs; however, it remains elusive how WS-derived iPSCs behave and whether they are able to mimic the disease-specific phenotype. The present study was designed to address these issues. Unexpectedly, we found that a specific WS fibroblast line of homozygous truncation mutation was difficult to be reprogrammed by using the Yamanaka factors even under hypoxic conditions due to their defect in induction of hTERT, the catalytic unit of telomerase. Ectopic expression of hTERT restores the ability of this WS fibroblast line to form iPSCs, although with a low efficiency. To examine the phenotype of WRN-deficient pluripotent stem cells, we also generated WRN knockout human embryonic stem (ES) cells by using the CRISPR/Cas9 method. The iPSCs derived from WS-hTERT cells and WRN-/- ESCs are fully pluripotent, express pluripotent markers and can differentiate into three germ layer cells; however, WS-iPSCs and WRN-/- ESCs show S phase defect in cell cycle progression. Moreover, WS-iPSCs and WRN-/- ESCs, like WS patient-derived fibroblasts, remain hypersensitive to topoisomerase inhibitors. Collectively, WS-derived iPSCs and WRN-/- ESCs mimic the intrinsic disease phenotype, which may serve as a suitable disease model, whereas not be good for a therapeutic purpose without gene correction.

Diversity-oriented synthesis of imidazo[2,1-a]isoquinolines.

Herein, we report an efficient and practical strategy for the synthesis of five types of imidazo[2,1-a]isoquinolines via Cp*RhIII-catalyzed [4+2] annulation of 2-arylimidazoles and α-diazoketoesters, whose structural and substituted diversity at 5- or 6-position can be precisely controlled by the α-diazoketoester coupling partners. Compared with previous reports, in this study, we merged two attractive C-C cleavage strategies (retro-Claisen and decarboxylation) into the classical C-H functionalization/condensation process by choosing appropriate ester groups (-COOEt, -COOtBu or -COOiPr) or inexpensive additives (HOAc or KOAc). Moreover, the synthetic efficacies of these methods were demonstrated by the concise synthesis of several bioactive compounds and the late-stage modification of representative drugs.